Inhibition of glucocorticoid‐induced apoptosis by the expression of antisense gene of mitochondrial ATPase subunit 6

FEBS Letters

Oguma, Takemi¹  Tsujimoto, Kyoko¹  Matsuki, Yasunori¹  Takayama, Eiji¹  Sato, Masaki¹  Tadakuma, Takushi¹ 

[1] Department of Immunology and Parasitology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan

关键词: Dexamethasone-induced apoptosis;    ATP synthesis;    Antisense cDNA;    FoF1 ATPase;    Functional cloning assay;    BSD;    blasticidin S hydrochloride drug-resistant;    Dex;    dexamethasone;    DIARG;    dexamethasone-induced apoptosis-related gene;    DiOC6(3);    3;    3′-dihexyloxacarbocyanine iodide;    GC;    glucocorticoid;    PI;    propidium iodide;    PS;    phosphatidylserine;    Py;    polyoma virus;    ΔΨ m;    mitochondrial membrane potential;   

DOI  :  10.1016/S0014-5793(00)01816-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

To isolate the apoptosis-linked genes involved in the cell death of thymocytes induced by glucocorticoids, we developed a functional cloning assay. Murine CD4⁺CD8⁺ thymic cell line 2-257-20 cells were transfected with cDNA expression libraries obtained from a dexamethasone-resistant cell line. The transfected cells were selected in the presence of dexamethasone, and the plasmids which episomally expanded were then extracted from the surviving cells. One of the rescued cDNAs was found to be an antisense cDNA fragment identical to the mouse mitochondrial ATPase 6 gene. In the stable transfectants with the ATPase 6 antisense gene, the induction of apoptosis by dexamethasone was significantly delayed. Furthermore, the ATP synthesis in these transfectants was also reduced to some extent. ATPase 6 is a subunit of F_oF₁ ATPase and our results support that ATP synthesis from the mitochondria is necessary for the induction of apoptosis induced by glucocorticoids.

【 授权许可】

Unknown